The Hummingbirds' Foundation for M.E. (HFME) is fighting for the recognition of M.E.,
and for patients to be accorded the same basic human rights as those with similar
disabling and potentially fatal neurological diseases such as M.S.

An important note:

Before reading the research/advocacy information given in the links below, please be aware of the following facts:

1.Myalgic Encephalomyelitis and ‘Chronic Fatigue Syndrome’ are not synonymous terms. The overwhelming majority of research on ‘CFS’ or ‘CFIDS’ or ‘ME/CFS’ or ‘CFS/ME’ or ‘ICD-CFS’ does not involve M.E. patients and is not relevant in any way to M.E. patients. If the M.E. community were to reject all ‘CFS’ labelled research as ‘only relating to ‘CFS’ patients’ (including research which describes those abnormalities/characteristics unique to M.E. patients), however, this would seem to support the myth that ‘CFS’ is just a ‘watered down’ definition of M.E. and that M.E. and ‘CFS’ are virtually the same thing and share many characteristics.

A very small number of ‘CFS’ studies refer in part to people with M.E. but it may not always be clear which parts refer to M.E. The A warning on ‘CFS’ and ‘ME/CFS’ research and advocacypaper is recommended reading and includes a checklist to help readers assess the relevance of individual ‘CFS’ studies to M.E. (if any) and explains some of the problems with this heterogeneous and skewed research.

In future, it is essential that M.E. research again be conducted using only M.E. defined patients and using only the term M.E. The bogus, financially-motivated disease category of ‘CFS’ must be abandoned.

2. The research referred to on this website varies considerably in quality. Some is of a high scientific standard and relates wholly to M.E. and uses the correct terminology. Other studies are included which may only have partial or minor possible relevance to M.E., use unscientific terms/concepts such as ‘CFS,’ ‘ME/CFS,’ ‘CFS/ME,’ ‘CFIDS’ or Myalgic ‘Encephalopathy’ and also include a significant amount of misinformation. Before reading this research it is also essential that the reader be aware of the most commonly used ‘CFS’ propaganda, as explained in A warning on ‘CFS’ and ‘ME/CFS’ research and advocacyand in more detail in Putting research and articles on Myalgic Encephalomyelitis into context.

Cardiac and cardiovascular research,

Since the Nightingale Research Foundation's publication in 1992 of its textbook, The Clinical and Scientific Basis of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome, there has been a tendency by some individuals and organizations to assume that M.E. and CFS are the same illness. Over the course of two International Association of Chronic Fatigue Syndrome (IACFS, formerly the American Association of CFS) conferences, there have been suggestions that the name CFS be changed to M.E., while retaining the CFS definitions as a basis for such change. This does not seem to me to be a useful initiative: it would simply add credence to the mistaken assumption that M.E. and CFS represent the same disease processes. They do not.

M.E. is a clearly defined disease process. CFS by definition has always been a syndrome

At one of the meetings held to determine the 1994 U.S. Centers for Disease Control and Prevention (CDC) definition of CFS, in response to my question from the floor, Dr. Keiji Fukuda stated that numerous M.E. epidemics he cited the Los Angeles County Hospital epidemic of 1934, the Akureyri outbreak of 1947-48 and the 1955-58 Royal Free Hospitals epidemics-- were definitely not CFS epidemics. Dr. Fukuda was correct.

[Contains details of the many vascular absnormalities seen in M.E., and explains how these can be tested for.]

‘Do not for one minute believe that CFS is simply another name for Myalgic Encephalomyelitis (M.E.). It is not. Though CFS is based upon a typical M.E. epidemic, in my opinion it has always been a confused and distorted view of reality. The invention of Chronic Fatigue Syndrome has to be one of the most curious cases of inventive American scientific imperialism that one could imagine. It is my opinion that the CDC 1988 definition of CFS describes a non-existing chimera based upon inexperienced individuals who lack any historical knowledge of this disease process. The CDC definition is not a disease process.’

The physician and patient alike should remember that CFS is not a disease. It is a chronic fatigue state as described in four definitions starting with that published by Dr. Gary Holmes of the CDC and others in 1988 (Holmes, Kaplan, Gantz, et al., 1988; Holmes, Kaplan, Schonberger, et .al., 1988). The definition created by Lloyd, Hickie, Boughton, Spencer, and Wakefield (1990) is also widely used in Australia. There are two subsequent definitions. The Oxford definition of 1991 (Sharpe et al., 1991) and the 1994 NIH/CDC definitions (Fukuda et al., 1994) are basically, with a few modifications, copies of the first definition. Where the one essential characteristic of ME is acquired CNS dysfunction, that of CFS is primarily chronic fatigue. By assumption, this CFS fatigue can be acquired abruptly or gradually. Secondary symptoms and signs were then added to this primary fatigue anomaly. None of these secondary symptoms is individually essential for the definition and few are scientifically testable. Despite the list of signs and symptoms and test exclusions in these definitions, patients who conform to any of these four CFS definitions may still have an undiagnosed major illness, certain of which are potentially treatable.

Although the authors of these definitions have repeatedly stated that they are defining a syndrome and not a specific disease, patient, physician, and insurer alike have tended to treat this syndrome as a specific disease or illness, with at times a potentially specific treatment and a specific outcome. This has resulted in much confusion, and many physicians are now diagnosing CFS as though it were a specific illness. They either refer the patient to pharmaceutical, psychiatric, psychological, or social treatment or simply say, "You have CFS and nothing can be done about it."

[Contains details of the many vascular absnormalities seen in M.E., and explains how these can be tested for.]

"A good memory demands normal functioning of almost all areas of the cerebral cortex, the basal nerve centres of the mid brain (eg the thalamus and hippocampus) and their interconnecting pathways through the brain stem. Fluctuations of metabolic activity in these areas (often made worse by physical and mental exhaustion) have been reported in SPECT scans of patients with ME,(2) the vast majority of whom complain of difficulty with short-term memory."

There is ample evidence that M.E. is primarily a neurological illness. It is classified as such under the WHO international classification of diseases (ICD 10, 1992) although non neurological complications affecting the liver, cardiac and skeletal muscle, endocrine and lymphoid tissues are also recognised. Apart from secondary infection, the commonest causes of relapse in this illness are physical or mental over exertion 1. And, on follow up over decades (rather than weeks or months), the average person so disabled is found to be functioning (as a student, employee or parent for example) dangerously near their energy limits. The prescription of increasing exercise is such a situation (or in the early stage of the illness when the patient desperately needs rest) can only be counter-productive.

"The number likely to be affected by the post-polio syndrome has been calculated as between 200-270/100,000 currently[7], but no account has been taken of survivors from non-paralytic polio which could easily double that figure. Possible costing for ME support has been based on 3 times the cost of maintenance for multiple sclerosis on the supposition that ME is 3 times as common[4]. The only costs that we can be sure of are those derived from the failure of appropriate management, and of inappropriate assessments which waste vast sums of money and medical time while allowing patients to deteriorate unnecessarily.[16]

Research workers must be encouraged and appropriately funded to work in this field. However they should first be directed to papers published before 1988, the time at which all specialised experience about poliomyelitis and associated infections seem to have vanished mysteriously![11,12,13]"

This essential feature of M.E. is characterised by a unique form of paralytic muscle weakness whereby muscles perform normally to begin with but after even a minor degree of physical effort; three, four or five days, or longer, elapse before full muscle power is restored. This is quite distinct from the ‘chronic fatigue’ seen in many other illnesses.

Fatigue’ and feeling ‘tired all the time’ are not at all the same thing as the very specific type of paralytic muscle weakness or muscle fatigue which is characteristic of M.E. (and is caused by mitochondrial dysfunction) and which affects every organ and cell in the body; including the brain and the heart. This causes – or significantly contributes to – such problems in M.E. as; cardiac insufficiency (a type of heart failure), orthostatic intolerance (inability to maintain an upright posture), blackouts, reduced circulating blood volume (and pooling of the blood in the extremities), seizures (and other neurological phenomena), memory loss, problems chewing/swallowing, episodes of partial or total paralysis, muscle spasms/twitching, extreme pain, problems with digestion, Raynaud’s phenomenon, vision disturbances, breathing difficulties, and so on. These problems are exacerbated by even trivial levels of physical and cognitive activity, sensory input and orthostatic stress beyond a patient’s individual post-illness limits leaving M.E. patients extremely disabled (Bassett 2009, [Online]).

People with M.E. are experiencing a form of heart failure which can be exacerbated by even relatively low levels of activity. Many patients are housebound and bedbound and often are so ill that they feel they are about to die. Some M.E. patients do die due to overexertion. People with M.E. would give anything to instead only be severely ‘fatigued’ or tired all the time.

Fatigue or post-exertional fatigue (or malaise) may occur in many different illnesses such as various post-viral fatigue states or syndromes, Fibromyalgia, Lyme disease, and many others – but what is happening with M.E. patients is an entirely different (and unique) problem of a much greater magnitude. These terms are not accurate or specific enough to describe what is happening in M.E.

The paralytic muscle weakness seen in M.E. affects all muscles including the heart and causes what is commonly known as exercise intolerance; that patients relapse with excessive physical and cognitive exertion, as well as with orthostatic stress. These features are a core part of what M.E. is as they are responsible for causing much of the symptomatology and disability associated with the disease (Hyde 2006, [Online]) (Hooper 2006, [Online]) (Hooper & Marshall 2005a, [Online]) (Hyde 2003, [Online]) (Dowsett 2001, [Online]) (Hooper et al. 2001, [Online]) (Dowsett 2000, [Online]) (Dowsett 1999a, 1999b, [Online]) (Dowsett 1996, p. 167) (Dowsett et al. 1990, pp. 285-291) (Dowsett n.d., [Online]).

Doctors who have experience with M.E. (and can tell the difference between authentic M.E. and various unrelated fatigue states) and the leading M.E. experts all concur; physical, cognitive or orthostatic overexertion can have many harmful effects on patients both in the short- and long-term. The following comments which illustrate this point are provided by some of the world’s leading M.E. experts, all of whom have been specialising in M.E. for many years and each of whom has seen literally thousands of M.E. patients;

1. Dr Melvin Ramsay, a UK doctor who specialised in M.E. for more than thirty years, from the Royal Free Hospital M.E. outbreak of 1955 until his death in 1990, and who is credited with having written some of the most accurate description of the illness to date, explains, ‘The degree of physical incapacity varies greatly, but the [level of severity] is directly related to the length of time the patient persists in physical effort after its onset; put in another way, those patients who are given a period of enforced rest from the onset have the best prognosis. Those who are given complete rest from the onset do well. Those whose circumstances make adequate rest periods impossible are at a distinct disadvantage, but no effort should be spared to give them the all-essential basis for successful treatment. Since the limitations which the disease imposes vary considerably from case to case, the responsibility for determining these rests upon the patient. Once these are ascertained the patient is advised to fashion a pattern of living that comes well within them’ (Ramsay 1986, [Online]).

2. Dr. Elizabeth Dowsett explains, ‘There is ample evidence that M.E. is primarily a neurological illness although non neurological complications affecting the liver, cardiac and skeletal muscle, endocrine and lymphoid tissues are also recognised. Apart from secondary infection, the commonest causes of relapse in this illness are physical or mental over exertion. The prescription of increasing exercise is such a situation (or in the early stage of the illness when the patient desperately needs rest) can only be counter-productive’ and ‘This illness is distinguished from a variety of other post-viral states by an unique clinical and epidemiological pattern characteristic of enteroviral infection. Prompt recognition and advice to avoid over-exertion is mandatory’ and ‘The prescription of increasing exercise can only be counter-productive.’

The brain has often been likened to a computer. However, there are fundamental differences in its essential function of processing, comparing and storing information. Unlike a computer, which can be switched on and off and is programmed to give set answers to a single question, the chemical transmitter bridging the synapse introduces a variability into the on-going message and "Neuronal Plasticity" into the receiving/transmitting network. It has been shown that similar modifications in response may be induced by virus infection. The brain contains some 100 billion neurons connected to some 10,000 relay stations and this enormous electrical activity creates a massive need for energy, using up 20% of the entire body's demand for oxygen and glucose. Recent studies of the brain stem by SPECT scan, indicate hypoperfusion and low metabolic activity in subjects with M.E.

Modern research indicates disturbed metabolism in many areas essential to motor control in the brain stem of patients with M.E., the majority of whom have evidence of inco-ordinated muscle twitching after slight exertion.

A good memory demands normal functioning of almost all areas of the cerebral cortex, the basal nerve centres of the mid brain (eg the thalamus and hippocampus) and their interconnecting pathways through the brain stem. Fluctuations of metabolic activity in these areas (often made worse by physical and mental [overexertion]) have been reported in SPECT scans of patients with M.E., the vast majority of whom complain of difficulty with short-term memory (n.d.c, [Online]).

Dr Dowsett states about M.E. patients that, ‘20% have progressive and frequently undiagnosed degeneration of cardiac muscle which has led to sudden death following exercise.’

According to Dr. Elizabeth Dowsett, any M.E. patient can also be stopped from deteriorating further and at least stabilised (if not in time experiencing some level of improvement) through receiving appropriate care and being allowed to get the needed level of rest (providing that the patient has not already been exposed to unrecoverable levels of overexertion) (Dowsett & Ramsay et al. 1990) (Dowsett 2000, [Online]) (Dowsett 2001a, [Online]) (Dowsett n.d.b., [Online]). Dr. Elizabeth Dowsett also explains that:

Scientific discoveries recently reported, indicate that embryonic stem cells left over from foetal development, remain in the brain tissue during adult life and are capable of “running repairs” (thus patients are able to recover after head injury, stroke and relapse in ME). However, overuse of these repairs, as in ME (when the patients are overstressed [overexexerted] physically or mentally) will cause unnecessary deterioration which may then become irreparable. Intervention in the form of financial, rehabilitation and nutritional support can do much to prevent the physical, occupational and other deterioration in the quality of life for a large group of patients now between 40 and 60 years of age, to say nothing of educational loss in children.

HEALTH SERVICE INTERVENTIONS: It is sad to read that these are said to be of dubious priority in the present state of the NHS when it is known that the correct type of rehabilitation can stabilise the illness. This requires access to local facilities without discrimination against patients with a diagnosis of ME, together with a domiciliary nursing service for the bed-bound who are unable to travel ( 2002b, [Online]).

3. Dr Byron Hyde explains in his M.E. textbook that it has been found that those patients with M.E. who returned to work soon after becoming ill or while they were still seriously or severely ill – instead of having an extended period of rest and recovery – are at risk of causing an abnormal increase in damage ‘to a heart muscle already vulnerable and under attack from an acute viral infection’ and that those who do not, or cannot, rest in the early stages of M.E. potentially create ‘a physical injury to the myocardium, cardiac pacemaker cells or their autonomic control.’ Dr Hyde explains that:

This is not just clinical supposition, there is a strong basic for this belief of work or exercise potentiated heart damage in the literature. It is well known that enteroviruses may cause chronic cardiac disease as well as major neurological injury. Kandolf states that "enteroviruses are capable of causing dilated cardiomyopathy of sudden onset or lead to a variety of common arrhythmias." Utilizing mouse models, Wilson and again Reyes demonstrated that Coxsackie infected [enterovirus infected] mice, forced to swim to the point of exhaustion during the acute phase of infection, developed chronic heart disease whereas Coxsackie infected mice who were allowed to rest during the acute phase, did not develop chronic heart disease.

M.E. represents a possibility of serious cardiac injury primarily in patients who exercise or maintain exhaustive work efforts during the onset of their illness. It is possible that some of these patients who die and other that develop major cardiac changes are never recognised as M.E.

With both CNS and CVS disease, chronicity may be provoked by maintaining strenuous exercise and work levels.. Early patient activation may represent serious cardiovascular danger to patients [with M.E.]. The strange concept of waiting 6 months to diagnose a classical case of M.E. [brought about by the confusion between M.E. and ‘CFS’] is unnecessary and fraught with potential danger to the patient. Such a diagnostic delay may create legal consequences for the physician. Physicians who take an early aggressive approach in physically activating these acute stage patients may do so at both their and their patient’s peril (Hyde & Jain 1992a, pp. 375-383).

M.E. is an infectious neurological disease and represents a major attack on the central nervous system (CNS) by the chronic effects of a viral infection. The world’s leading M.E. experts, namely Ramsay, Richardson, Dowsett and Hyde, (and others) have all indicated that M.E. is caused by an enterovirus. (This also includes doctors such as A. Gilliam, W.H. Lyle, Elizabeth Bell of Ruckhill Hospital, James Mowbray of St Mary’s, and Peter Behan). The evidence which exists to support the concept of M.E. as an enteroviral disease is compelling (Hyde 2007, [Online]) (Hyde 2006, [Online]).

Dr Hyde explains that enteroviral infections are able to cause:

a chronic host infection

major or no cardiac disease depending on the virulence of the subtype

cardiac injury dependent upon the sex of the patient and of the level of physical activity of the patient during the acute or infectious stage

An enterovirus would also explain the; age variation, sex variation, obvious resistance of some family members to the infection and the effect of physical activity (particularly in the early stages of the illness) in creating more long-term/severe M.E. illness in the host (Hyde & Jain 1992a, p. 40). There is also the evidence that; M.E. epidemics very often followed polio epidemics, M.E. resembles polio at onset, serological studies have shown that communities affected by an outbreak of M.E. were effectively blocked (or immune) from the effects of a subsequent polio outbreak, evidence of enteroviral infection has been found in the brain tissue of M.E. patients at autopsy, and so on (Hyde 2007, [Online]) (Hyde 2006, [Online]) (Hyde 2003, [Online]) (Dowsett 2001a, [Online]) (Dowsett 2000, [Online]) (Dowsett 1999a, 1999b, [Online]) (Hyde 1992 p. xi) (Hyde & Jain 1992 pp. 38 - 43) (Hyde et al. 1992, pp. 25-37) (Dowsett et al. 1990, pp. 285-291) (Ramsay 1986, [Online]) (Dowsett & Ramsay n.d., pp. 81-84) (Richardson n.d., pp. 85-92) (Richardson 1999, [Online]).

Dr Byron Hyde, also explains that the vascular and cardiac dysfunctions seen in M.E. are often the most obvious set of dysfunctions when looked for, and are the cause of a significant number of M.E. symptoms:

The subject of vascular pathology is not new. The fact of the children dying of a Parkinsonian-like vascular injury to the basal ganglia in Iceland during the Akureyri M.E. Epidemic is an obvious indication of the CNS vascular effects in M.E. Vasculitis has been well documented by Dr. E. Ryll in his description of the epidemic in the San Juan Mercy, Sacramento California Hospital in 1975. He described this M.E. epidemic as an epidemic vasculitis. He was correct. Following my 21 years of examining M.E. patients and 16 years of subjecting M.E. patients to brain imaging techniques, it has become obvious to me that we are dealing with both a vasculitis and a change in vascular physiology. Numerous other physicians have supported this finding.

The recent interpretation of the cause of Multiple Sclerosis (MS), as an injury of the microvasculization causing the injury of the schwann cells that in turn causes the demyelination injuries of MS has been added to that of paralytic poliomyelitis as an essential vascular injury. Paralytic poliomyelitis was thought to be a primary injury to the anterior horn cells of the spinal cord but is now recognized as a vasculitis injuring the circulation to the anterior horn cells. Poliomyelitis is generally a non-progressive, specific site injury, although post-polio syndrome with demonstration of subcortical brain changes has challenged that belief. MS is a recurrent more fulminant physiological vascular injury. M.E. appears to be in this same family of diseases as paralytic polio and MS. M.E. is definitely less fulminant than MS but more generalized. M.E. is less fulminant but more generalized than poliomyelitis. This relationship of M.E.-like illness to poliomyelitis is not new and is of course the reason that Alexander Gilliam, in his analysis of the Los Angeles County General Hospital M.E. epidemic in 1934, called M.E. atypical poliomyelitis (2007, [Online]).

Dr Byron Hyde also writes, ’I have some M.E. patients with a circulating red blood cell volume less than 50% of expected and a very large number with the range of 60% to 70%. What this test means is that blood is pooling somewhere in the body and that this blood is probably not available for the brain. When blood flow to the heart decreases sufficiently, the organism has an increased risk of death. Accordingly, the human body operates in part with pressoreceptors that protect and maintain heart blood supply. When blood flow decreases, pressoreceptors decrease blood flow to noncardiac organs and shunt blood to the heart to maintain life. This, of course, robs those areas of the body that are not essential for maintaining life and means the brain, muscles, and peripheral circulation are placed in physiological difficulty.’ This physiological difficulty is exacerbated by physical and mental activity and orthostatic stress.

Dr Byron Hyde goes on to say that, ‘In MRI spectography of arm muscle of M.E. patients, it has been shown that because of an abnormal buildup of normal metabolites, the muscle cell actually shuts down to prevent cell death.’ Dr Hyde explains that this is what is happening to the true M.E. patient’s cell physiology in the brain, and in muscle as a result of certain levels of physical and mental activity; there is ‘cell field shutdown’ to prevent the death of the cell (Hyde 2003, [Online]).

Possibly due to the fact that some Fibromyalgia patients can be improved by a gradual increase in exercise, or possibly due to the so called protestant ethic that all you have to do to get better is to take up your bed and walk, some physicians have extended the concept of passive or forceful increased exercise to Myalgic Encephalomyelitis patients. This is a common and potentially dangerous, even disastrous misconception. If the M.E. patient conforms to the guidelines set out in this definition, the insurance company can only make the patient worse by instituting progressive aggressive forced physical and intellectual activity. M.E. is a variable but always, serious diffuse brain injury and permanent damage can be done to the M.E. patient by non-judicious pseudo-treatment (2007, [Online]).

We also have ample evidence from other doctors who have a significant involvement with M.E. patients (although for various reasons they cannot be considered M.E. experts, as such), indicating that M.E. patients have an abnormal and negative response to exertion. This includes the following:

1. In April 2003, Arnold Peckerman MD from New Jersey reported findings to the annual meeting of the American Physiological Society that demonstrated via a sophisticated test that after exercise, the heart of those with M.E.* pumped less blood than it did at rest. Peckerman is on record as saying that it is a ‘progressive disease’ and that, ‘Basically we are talking about heart failure. A drop in [blood pumped by the heart] during exercise is not a typical response.’

This important research showed that, without exception, every disabled M.E. patient is in heart failure. The New Jersey team found evidence of the “Q” problem in M.E. “Q” stands for cardiac output in litres per minute. In M.E. patients, Q values correlated, with great precision, with the level of disability. Q was measured using impedance cardiography, a clinically validated and Government agency-recognised algorithm. (Impedance cardiography is not experimental.)

Normal people pump 7 litres of blood per minute through their heart, with very little variance, and when they stand up, that output drops to 5 litres per minute (a full 30% drop, but this is normal). Those two litres are rapidly pooled in the lower extremities and capacitance vessels. Normal people do not sense the 30% drop in cardiac output when they stand up because their blood pressure either stays normal or rises when they stand up, the body will defend blood pressure beyond anything else in order to keep the pulse going.

What the New Jersey team found in people with M.E. was astonishing – when these disabled patients stand up, they are on the edge of organ failure due to extremely low cardiac output as their Q drops to 3.7 litres per minute (a 50% drop from the normal of 7 litres per minute).

The disability level was exactly proportional to the severity of their Q defect, without exception and with scientific precision. In this Peckerman study, the data on the disabled M.E. patients reveals that even when they are lying down, their Q is only 5 litres per minute. The lower the Q, the more time the patient will spend lying down because lying down is the only time they come close to having sufficient cardiac output to survive (Peckerman et al. 2003, [Online]) (Hooper et al. 2007, [Online]) (Web M.D. 2009, [Online]).

2. Dr Cheney (following on from the Peckerman study) explained recently that because it takes more metabolic energy for the heart to relax and fill with blood than it does for it to squeeze and pump blood, the hearts of people with M.E. don’t fill with the proper amount of blood before they pump which is what causes the reduced cardiac output and many of the symptoms of M.E. and much of the disability of M.E. (The following summary of Cheney’s work (most of which was made public only in the form of recorded lectures) is taken from the Corporate Collusion paper by Professor Malcolm Hooper et al.)

Cheney comments that patients with M.E. suffer from cardiac problems since they cannot pump sufficient blood to the heart. He explains that the inability of very ill patients to stand up is the body protecting itself from cardiac stress and possible death. Cheney explains that if patients draw down their lifestyle to live within the means of the reduced cardiac output, then progression into congestive cardiac failure (CCF) is slowed down, but if things continue to progress, a point will be reached where there is no adequate cardiac output, and dyspnoea will develop, with ankle oedema and other signs of congestive cardiac failure. In order to stay relatively stable, it is essential for the patient not to create metabolic demand that the low cardiac output cannot match. Attempts to push beyond limits will cause injury or death.

Cheney also explains that M.E. patients have a high heart rate but a low cardiac output. In M.E. there is a cardiac dimension that is independent of (but not excluding) autonomic function or blood volume. A mismatch between metabolic demand and cardiac output, even very briefly, will kill. If the cardiac output goes down, in order not to die, there is a rise in noradrenergic tone (also involving the adrenal glands) to bring the output back up. This is a serious problem, because when the adrenals are exhausted, there will be low cardiac output. There is no such thing as an M.E. patient who is NOT hypothyroid: this has nothing to do with thyroid failure, but everything to do with matching metabolic demand and cardiac output.

Half of patients exhibit atrial cavitation, and when these patients stood up, the filling volume collapsed. M.E. patients "squeeze the hell" out of their left ventricle, resulting in a "whopping" 70% increase in left ventricular wall motion thickness. The reason why patients are squeezing so hard is because they do not have enough energy to fill the chambers of the heart properly so they are trying to compensate by squeezing a lot harder (ie. the way patients are compensating for this loss of cardiac output is by squeezing the left ventricle much harder). There are significant consequences of this. One consequence is that M.E. patients become asynchronised (ie. the heart can be filling and ejecting at the same time). If out of synchrony, the ventricle cannot cope, so cardiac output is severely degraded.

Cheney posits that when faced with a low Q, the body sacrifices tissue perfusion in order to maintain blood pressure: ie. microcirculation to the tissues of the body is sacrificed to maintain blood pressure so that the person does not die in the face of too low a cardiac output. This compensation is what is going on in the M.E. patient. Cheney states that it is important to note that the body does not sacrifice tissue perfusion equally across all organ systems: instead, it prioritises the order of sacrifice and one can observe the progression of M.E. in a patient by noting this prioritisation.

Two organ systems in particular have a protective mechanism (the Renin Angiotensin System, or RAS) against restricted tissue perfusion: the lung and the kidneys. These organs can sustain the greatest degree of Q problems because of this extra protection. Additionally, the heart and the brain also have this extra protection, even in the face of an extremely low Q. Therefore the lung, the brain, the kidneys and the heart are a bit more protected from a drop in Q than the liver, the gut, the muscles and the skin.

a. The first to be affected is the skin: if the microcirculation of the skin is compromised, several problems can arise. The body cannot thermoregulate anymore: the patient cannot stand heat or cold and if the core temperature rises, the patient will not be able to sleep and the immune system will be activated. In order to regulate that problem, the body will kick in thyroid regulation which will down-regulate in order to keep the body temperature from going too high. The patient then develops compensatory hypothyroidism, which means that now the patient will have trouble with feeling cold. Also, the body will not be able to eliminate VOCs (volatile organic compounds), which are shed in the skin’s oil ducts, so VOCs build up in the body’s fat stores and the patient becomes progressively chemically poisoned by whatever is present in the environment.

b. The second effect: the next microcirculation to be sacrificed is that to the muscles and the patient will have exercise intolerance. If things get still worse, the patient begins to experience pain in the muscles. If the microcirculation to the joints becomes compromised, the patient starts to have arthralgia linked to this circulatory defect.

c. The next system to be compromised is the liver and gut. One of the first things the patient may notice in this stage of disease progression is that there are fewer and fewer foods that can be tolerated, partly because microcirculation is necessary for proper digestion. Also the body will not secrete digestive juices so whatever food is tolerated will not be digested: if food cannot be digested, there will be peptides that are only partially digested and therefore are highly immune-reactive; they will leak out of the gut into the bloodstream, resulting in food allergies or sensitivities. The body will be unable to detoxify the gut ecology, so the gut will begin to poison the patient, who will feel as if poisoned, with diarrhoea, constipation, flatulence and other gut problems.

d. The fourth affected system is the brain: Cheney posits that there is a devastating effect in the brain as a result of liver / gut dysfunction, which can quickly toxify the brain, resulting in disturbances of memory and of processing speed. Also, the hypothalamus begins to destabilise the patient from the autonomic nervous system perspective. In all probability, the brain and heart suffer simultaneous compromise, but patients usually notice the brain being affected much earlier than the heart – this is because heart muscle cells have the greatest mitochondrial content of any tissue in the body, so when the mitochondria are impaired, the heart muscle has the greatest reserve. Even if the patient is sedentary with not too much demand on the heart, they can still think and make great demands on the brain, and energy is energy, whether it is being used physically or cognitively.

The fifth affected system is the heart: Cheney posits that the effect of compromised microcirculation upon the heart has an “a” part and a “b” part: part “a” is the manifestation of microcirculation impairment and part “b” is “the event horizon”.

Part “a”: manifestation of microcirculation impairment: the initial manifestation of microcirculatory impairment of the heart is arrhythmia with exercise intolerance: when the patient goes upstairs, more cardiac output is needed but the patient cannot sustain it. When there are even more severe microcirculatory problems, the patient starts to get chest pain as the myocardial cells die because they cannot get adequate oxygen.

Part “b”: the event horizon: (once this line is passed, there is no going back): Cheney’s view is that when the microcirculation defect within the heart itself begins to impact Q, a vicious circle begins – microcirculation impairment reduces the Q, which produces more microcirculation impairment, which produces even more Q problems, so down goes the patient into the next phase of cardiac failure, which involves the lungs.

The sixth affected system is the lung and kidney: this leads to congestive heart failure and pulmonary oedema, then the kidney is affected (the kidney is the last to go because it has the RAS back-up system). Combined with liver impairment, this stage is known as hepatorenal failure. A patient will know if s/he eventually loses the ability to compensate if, when they lie down, they are short of breath. Cheney’s view is that cardiac muscle has lost power because the mitochondria are dysfunctional (ie. there is an energy-production problem in the cells).

The red blood cells of patients with M.E. have been found to be deformed. When deformed, they cannot get through the capillary bed, causing pain. An indication of such deformity is a drop in the sedimentation rate (SED, or ESR) and Cheney (along with Dr Hyde and other M.E. experts) has observed that when measured in a laboratory, M.E. patients’ sedimentation rate is the lowest he has ever recorded, which confirms that M.E. patients have an induced haemoglobinopathy. Cheney has stated that the M.E. patients with the lowest sedimentation rate may have the greatest degree of pain. The more deformed the red blood cells, the more pain may be experienced. Some M.E. patients have a problem similar to that of sickle cell anaemia in this regard, and sickle cell patients have unbelievable pain. Cheney emphasises that it is bad enough when patients do not perfuse their muscles and joints (because of poor microcirculation) but it is even worse when red blood cells are so deformed that they can barely get through the capillaries or are blocked entirely. Cheney notes that in the Laboratory Textbook of Medicine, there are only three diseases that lower the sedimentation rate to that level: one is sickle cell anaemia (a genetic haemoglobinopathy); the second is M.E. (an acquired haemoglobinopathy) and the third is idiopathic cardiomyopathy. (The latter being one way in which the cardiac problems of M.E. are described.)

Cheney observes that in order to improve cardiac output, patients need to lie down, as this increases the cardiac output by 2 litres per minute. He notes that some patients need to lie down all the time to augment their blood volume in order to survive (Cheney 2006, [video recording]) (Peckerman et al. 2003, [Online]) (Hooper et al. 2007, [Online]).

Findings which showed mitochondrial dysfunction similar to mitochondrial encephalomyopathy also led Dr Cheney to comment, ‘The most important thing about exercise is not to have [patients with ME] do aerobic exercise. I believe that even progressive aerobic exercise is counter-productive. If you have a defect in mitochondrial function and you push the mitochondria by exercise, you kill the DNA’ (Williams 2004, [Online]).

Note that Dr Cheney cannot be said to be a M.E. expert, although he does deal primarily with M.E. patients and his comments on cardiac insufficiency can (and do) only relate to genuine M.E. patients as this finding is unique to M.E. patients. Unfortunately Cheney uses the terms ‘CFS’ and ‘CFIDS’ to refer to M.E. patients and, worse, unfortunately mixes in some medical and political facts about ‘CFS’ and ‘CFS’ patients (patients with diseases other than M.E.) into his 20 years of M.E. research. Thus not all of his work relates 100% to M.E. unfortunately. See: Is Cheney talking about M.E. or 'CFS'? for more information.

Dr Peckerman, like Cheney, has been involved in the study of the abnormalities unique to M.E. Unfortunately however he has used the terminology and definitions of ‘CFS’ and has included a vast amount of ‘CFS’ propaganda in his work. Thus while Dr Peckerman has some legitimate knowledge of the M.E. disease process, he cannot be considered a M.E. expert. Note also that both of these doctors do not use anything like the most severely affected M.E. patients in their research.

As these comments clearly indicate, the adverse response to physical activity in M.E. patients is not ‘medically unexplained’ – research has found a number of sound medical reasons why M.E. sufferers are so physically disabled and limited, and unable to maintain an upright posture. These include; evidence of damage to the central nervous system (and autonomic and sympathetic nervous systems, causing a loss of normal internal homeostasis), damage to cardiac muscle (and many other cardiac and cardiovascular abnormalities including evidence of cardiac insufficiency), abnormalities and damage to muscle, immune system abnormalities, respiratory abnormalities and also a variety of abnormalities at a cellular level (eg. mitochondrial defects).

It is also worth noting that none of these abnormalities can be explained by so-called ‘deconditioning’ – the supposed reason for the recommendation of therapies such as GET.

In this study, 100% of the ME/CFS participants showed abnormal oscillating T-waves at 24 hr. holter monitoring and 24% showed weakened function on the left side of the heart (abnormal cardiac dynamics). This is the side of the heart that pumps oxygenated blood to all of the body, except the lungs. Data, gathered from biopsies and a 24-hour electrocardiogram (EKG) Holter monitor, showed that patients exhibited evidence of cardiomyopathy or disease of muscle in the heart.

These researchers tracked EKGs over a 24-hour period with a Holter monitor device and documented abnormal T-waves. This wave measures electrical recovery after contraction of the left ventricle. A normal T-wave should be shaped like the rolling crest of a wave in water. In 100% of ME/CFS patients, Lerner and his associates documented T-wave Inversions and/or T-wave flattenings. This finding is so consistent, they suggest that the Holter results should be included as part of the CDC case definition; it distinguishes ME/CFS patients from those with fatigue or unexplained origin. This research holds the potential to distinguish ME/CFS patients from FM patients, from those with other pain syndromes who do not relapse with exertion, and from those with fatigue associated with depression, which is a group that also does not suffer relapse with exertion. This work offers hard evidence to back up ME/CFS patients' much disbelieved claim that exercise is harmful and causes disease progression in ME/CFS.

In Dr. Lerner's model, the weakened heart is aggravated by physical activity, accounting for the post-exertional sickness and accounting for the post-exertional sickness so common in this disease - including flu symptoms, chills, fevers and increasing weakness. Indeed, the cardiac connection is what is so ground-breaking about this research.

In experiments with mice, Dr. Lerner has shown that raised myocardial coxsackie viral titers accompany physical exertion in the mice. When the heart muscle tissue is infected, overactivity causes death of cardiac tissue and disease progression. This is in direct conflict with the U.S. government research conclusions that ME/CFS disease symptoms are caused by underactivity due to a sedentary lifestyle. Dr. Lerner advises resting the heart in order to "do no harm" and to prevent death of cardiac tissue.

Dr. Lerner and associates also have documented abnormal ejection fractions in ME/CFS. Normally, over half of the blood in the left ventricle is ejected when the left ventricle contracts (part of the heart that pumps oxygenated blood out to the body). In Dr. Lerner's ME/CFS subjects, the ejection fraction is sometimes decreased, an indication that not all the normally-expelled blood leaves the ventricle. Some patients had reduced ejection fractions at rest while others had an ejection fraction that decreased during exercise from 51% to 36%. In a normal subject, the ejection fraction will rise over 5% during exercise. Stationary or falling ejection fraction is abnormal in coronary artery disease or cardiac muscle disease. Declining ejection fractions are not seen in normal persons leading sedentary lives.

These cardiac abnormalities are hypothesized to be virally induced.

This model explains the John Hopkins' finding of Rowe et al in which ME/CFS patients exhibited abnormal response to upright tilt. Lerner argues that it is abnormal cardiac response of cardiomyopathy instead of abnormal neural response. Indeed, Dr. Lerner's thesis explains a myriad of phenomenon that other research has not. For example, it explains why patients relapse with exertion and why only physically active young persons may acquire the disease. It also explains why stress is a major aggravator in this disorder. Stress may aggravate both herpes viruses and heart conditions. It also explains the anti-viral lymphocyte enzyme system, the 2-5 A pathway, suggesting the presence of a chronic infection.

In short, Dr. Lerner's work explains why previously healthy, vigorous young adults fall ill with chronic cardiomyopathy due to viral infection and cannot exercise for fear of causing further heart damage. This is directly opposite to the work of Dr. Stephen Straus at National Institute of Health (NIH) whose theory states that ME/CFS is a psychiatric disorder. This new research of Dr. Lerner et al is both refreshing and insightful. Needless to say, it has also been long awaited.

The most acutely perceptive and pioneering work on CFS these days is happening in a quiet corner of the country, out of the CFS limelight. The work is being conducted by A. Martin Lerner, M.D., an infectious-disease specialist at Wayne State University, along with his colleagues in cardiology. The basic thesis of their well-documented research is that CFS is an infectious cardiomyopathy of single or multiple viral etiology -- a cardiomyopathy that in many cases is progressive and degenerative. According to the theory, CFS results when an initial infection with a virus, or a reactivation of a latent virus -- for example, EBV or CMV -- attacks cardiac tissue, producing exercise intolerance, the hallmark of CFS. The human cardiac myofiber becomes the site of persistent viral infection. The infection flares up when the infected person physically exerts him or herself.

In a normal subject, an ejection fraction will rise during exercise. They note that a stationary or falling ejection fraction is abnormal. Their work cites studies showing that declining ejection fractions are not seen in normal persons leading a sedentary life. Deconditioning and a sedentary lifestyle in normal subjects are not causes of decreasing or falling left ventricular ejection fractions. On the contrary, these cardiac abnormalities are likely virally induced: in some of the CMV patients, ejection fractions reverted to normal after anti-viral therapy with ganciclovir.

One plausible hypothesis of the pathophysiology of chronic fatigue syndrome (CFS) is a disorder of circulation. The present study examined whether cardiovascular homeostasis at rest and centrally-mediated hemodynamic responses to behavioral challenges are altered in CFS. Methods: Twenty-one patients fulfilling CDC criteria for CFS (18 women and 3 men) and 25 matched sedentary controls were evaluated in supine, standing, and sitting postures (resting homeostasis), and during the cold pressor test and simulated public speaking (stress responsivity). The measured responses, in addition to blood pressure and heart rate, included impedance cardiography-derived stroke volume and cardiac output. Patients with CFS were rated for illness severity on a 6-point scale using the New Jersey CFS diagnostic system. Results: As a group, patients with CFS displayed a similar cardiovascular functional status on most of the parameters. However, an observation was made that in patients with CFS, a lower stroke volume was highly predictive (r = -.72, p < .001) of illness severity. When divided into severe (N = 11) and less-than-severe (N = 10) groups, the severe CFS patients were found to have a lower stroke volume and cardiac output (p < .05) relative to a more moderate CFS group across three different postures. In response to the speech task, the less severe CFS group displayed attenuated blood pressure responses relative to a healthy control group (p < .05). A reduced blood pressure response to speech stressor in less severe CFS patients was attributable to a smaller increase in total peripheral resistance. In contrast, cardiovascular responses to the cold pressor test were not significantly different Conclusion: These findings suggest the possibility of a low flow circulatory state in the most severe cases of CFS. In patients with a less severe form of CFS, a diminished blood pressure response to a cognitive-behavioral (speech presentation), but not to an aversive-sensory (the cold pressor test) stressor may indicate a defect in the higher cortical modulation of cardiovascular autonomic control. In this latter group, situations may arise where a demand for blood flow to the brain may exceed the supply with a possibility of ischemia and a decrement of function.

[Note that the 'severe' patients in this study are in reality only mildly or moderately ill]

Even though post-exertional malaise is a hallmark feature of ME/CFS, exercise programs are often prescribed with little thought to the effect they may have on patients. The panel of experts for the ME/CFS clinical consensus document(1) stressed that a thorough evaluation of patients and their total illness burden, optimizing medical management, and a careful evaluation of pain generators and risk factors must be done before even considering an exercise program. As much care must be taken in prescribing appropriate exercise for ME/CFS patients as in prescribing pharmaceuticals.(5)

[Note that recovery may be incomplete in some patients even after 'days or weeks' as this chart states. Symptom execerbation or progression may in fact persist for many months or years following exertion, or may be irreversible. This website also does not support use of the inadequate term 'fatigue' to describe the symptomatology of ME]

Objective: Many symptoms of chronic fatigue syndrome (CFS), including severity of fatigue, are periodic, fluctuant and are inducible by physical and mental activities. Chest pain is a common symptom of CFS, like patients with syndrome X, an ion channel disorder. Symptoms in CFS such as fatigue, myalgia and headache bear striking resemblance with neurological disorders that affect ion channel function, such as periodic paralysis and familial hemiplegic migraine. Maintenance of normal transmembrane ionic equilibrium is an active, energy-dependent process, and constitutes an important share of the resting energy expenditure (REE). We wanted to compare and contrast the clinical profile of CFS patients with other neurological disorders that are known to affect ion channel function, and estimate REE in CFS. We also studied the myocardial perfusion in CFS by thallium201 SPECT scans to compare the results with Syndrome X. Methods: All patients who fulfilled the modified CDC criteria for CFS were included in our studies. For investigations that required the administration of radiopharmaceuticals (e.g. cardiac-thallium201 SPECT scans), patients between the age of 18 - 65 years were recruited after informed consent. A comparable group of healthy, sedentary volunteers were tested as controls in the REE study. Results: Fatigue was fluctuant in most patients with CFS. This was induced or worsened by physical activities (exercise), mental stress and chemicals that affect ion channel function (e.g. alcohol, quinine and anaesthetics). Significant perfusion defects were observed in the cardiac-thallium201 SPECT scans in 70% of CFS patients, similar to that described in patients with syndrome X. In a separate study, a significant number of CFS patients were found to have elevated REE as compared to the controls using total body potassium (TBK) as the refererence (REE TBK).4 Conclusion: Abnormal thallium201-cardiac SPECT scans in CFS similar to those described in syndrome X suggest a common mechanism for both these conditions. An abnormality of membrane ion channel function is considered the underlying mechanism in syndrome X. Increased REETBK; in a subgroup of CFS patients suggests that some CFS patients spend more energy in maintaining essential body function at the expense of the energy available for other physical activities. Since 30% of REE is expended to maintain physiological ion gradients in normal health, cell membranes that leak ions increase REETBK Elevated REE and abnormal cardiac perfusion scans in CFS provide the first objective and indirect support to our hypothesis that symptoms in CFS could be the result of an acquired abnormality of the voltage or ligand-gated ion channels. It is possible that such alteration of transmembrane ion traffic could affect normal receptor sensitivity to neurochemicals and neurohormones such as acetylcholine, serotonin or other monoamines, accounting for the neuroendocrine abnormalities previously documented in CFS.

The two groups had similar resting ejection fraction (EF). During maximal exercise, EF increased in controls, but declined in CFS patients. The decreases in EF tended to be greater in patients with more severe symptoms. Using a decline in EF as a criterion, 13 CFS patients (81 percent) and 0 control subjects had positive tests. There were no group differences in levels of exertion, as indicated by similar cumulative work output, maximal heart rate, and increases in lactate levels. A similar patter of changes in EF (i.e., increases in controls and declines in CFS patients) was observed in response to postural stress. Conclusions This study provides a preliminary indication of reduced cardiac function in some patients with CFS. It raises the possibility that some CFS patients may have cardiac disorders that are subtle enough to escape the current net of clinical cardiological diagnoses, but may be significant enough in some patients -- perhaps in conjunction with other factors -- to lead to the clinical syndrome of CFS. The researchers note that their findings may also be explained by abnormalities other than those with the heart, including problems with the distribution of cardiac output, reduced blood volume, and neurogenic and endocrinologic abnormalities. Accordingly, further studies capable of defining more precisely the causes of altered cardiac stress responses are required.

"Now, do CFIDS patients prefer to stand up or lie down? Of course, they prefer to lie down. Do you know why? "Do you know what your cardiac output does when you stand up? It drops 30%. In all humans, without exception. So very critical to this technology is that it's the only one that could be done upright [again, four positions on the tilt table are best; standing up and laying down at a minimum]. And what they found is absolutely astonishing, truly astonishing. When [disabled CFIDS patients] stand up, [they're] on the edge of organ failure due to low cardiac output."

"Peckerman's research team at the VA Medical Center in East Orange, N.J., used a sophisticated test to measure how well the heart pumps blood. They gave the test to 16 chronic fatigue syndrome patients, both before and after they exercised. They also tested four non-athletic volunteers. All of the patients' and volunteers' hearts' pumped normally during rest. After exercise, however, 13 of the 16 chronic fatigue [syndrome] patients' hearts pumped less blood than they did at rest.

"Basically we are talking about heart failure," Peckerman tells WebMD. "But chronic fatigue syndrome is a progressive disease. If we were able to detect this in its early stages, it is quite possible there might be a way to treat it."

Peggy Munson’s book ‘Stricken: Voices from the Hidden Epidemic of CFIDS’ is available from this site which also features Peggy’s Awareness day letters from

2003. Dr. Paul Cheney explained how the bodies of CFIDS patients are choosing between lower energy and life, or higher energy and death. On a physiological level, CFIDS patients live in a near-death suspension, making patients feel much like they are dying, not tired.

Dr. David Bell has studied the near-death feeling as it relates to blood volume. "[T]he vast majority of Bell’s CFIDS patients had 'extraordinarily' low circulating blood volume (a combination of plasma and the red blood cells via which the plasma delivers oxygen throughout the body)," writes About.com columnist Joan Livingston. "While his average patients ran about 70 percent of normal, several patients with Chronic Fatigue Syndrome (PWCs) had only half the blood volume of a healthy person, an amount so low that it would ordinarily cause shock and prove fatal in a car accident."

ABSTRACT. Chronic fatigue syndrome (CFS) is an illness associated with severe activity limitation and a characteristic pattern of symptoms despite a relatively normal physical examination and routine laboratory evaluation. The recent description of delayed orthostatic hypotension in patients with CFS, and previous findings of reduced red blood cell (RBC) mass in other patients with orthostatic hypotension not known to have CFS, led us to measure RBC mass and plasma volume in 19 individuals (15 female, four male) with well characterized, severe CFS. RBC mass was found to be significantly reduced (p < 0.001) below the published normal range in the 16 women, being subnormal in 15 (93.8%) of them as well as in two of the four men. Plasma volume was subnormal in 10 (52.6%) patients and total blood volume was below normal in 12 (63.2%). The high prevalence and frequent severity of the low RBC mass suggest that this abnormality might contribute to the symptoms of CFS by reducing the oxygen-carrying power of the blood reaching the brain in many of these patients.

Conclusion: Of the 19 patients reported here, abnormalities in blood volume were very common. The most common, found in 16 of 19 patients, was a reduction in red blood cell mass. Eleven subjects had low plasma volumes, and total circulating blood volume was subnormal in 12 of 19 subjects. In some individuals this abnormality was strikingly severe. Patient #15, for example, had an RBC mass of 12.9 mL/Kg, which is 46% of the expected normal, and a total blood volume of 35.8 mL/Kg, which represents 49.7% of the expected normal value (21). Her peripheral hematocrit was not impressively low at 33.8%, presumably because of the symmetrical reduction in both RBC mass and plasma volume. In other patients the plasma volume was normal or even elevated in the face of a low RBC mass, and in nqne of these patients was the RBC mass abnormality detected by conventional interpretation of the peripheral hematocrit.

All of the subjects in this study had symptoms of orthostatic intolerance which probably contributed to their activity restriction, but tilt table and autonomic nervous system testing was not carried out systematically in these individuals. Normal sitting blood pressures were recorded in all patients under office visit circumstances, except for relatively low values in three and a mildly elevated blood pressure in one. Some of these patients have been tested subsequently and found to have delayed orthostatic hypotension (12), which may be characteristic for CFS (11,12). In general, blood pressure measurements were not predictive of the results of circulating blood volume measurements.

I. Blood Volume Data. So far in our office we have measured the circulating blood volume in nearly fifty patients using the Chromium 51 method. It is essential that this method be employed (done in the nuclear medicine department of large University hospitals) as it is the only reliable method of assessing blood volume. There are two components of blood: the red blood cells and the plasma (fluid); everything else doesn't contribute much to the volume. The results are expressed as a function of body weight. Normal red blood cell mass should be between 23 and 28 ml/Kg, and the plasma volume should be between 40 and 52 ml/Kg. The total circulating blood volume is the sum of the two parts, and should lie between 60 and 80 ml/K.

Overall, about eighty percent of our patients with CFS have had either a low red blood cell mass, plasma volume, or both. Some patients have been extremely low, less than 50% of normal blood volume. To put this in perspective, if a healthy person were to bleed 40% of their volume out in a car accident it would likely be fatal. The loss in CFS is presumably gradual. The finding of decreased blood volume in CFS first came from Dr. David Streeten, and I am convinced it is accurate and will serve as a marker for the illness in some regard.

Abstract: To evaluate a possible cardiac pathophysiology of the chronic fatigue syndrome, we compared the resting cardiac function and exercise performance of 41 patients to those of an age-matched and sex-matched normal control group. Persistent fatigue following an acute apparently viral illness was the major complaint of all patients; none had specific cardiac symptoms nor abnormal physical findings. Electrocardiographic spatial patterns were normal in the patients, and there were no differences in the body surface sum of positive T-wave integrals between the patients (240 microV.x 10(2) ± 107 microV.s x10(2)) and control (244 microV.x 10(2) ± 108 microV.s x 10(2) subjects. Twenty-four hour ambulatory ECGs revealed no differences in sinus rates and incidences of ventricular dysrhythmias in the two populations. Left ventricular dimensions and systolic fractional shortening values were also similar in both groups; moreover none of the patients had segmental wall motion abnormalities. On graded exercise testing, 20 of 32 normal subjects achieved target (85 percent of age-maximum) heart rates, compared to four of 31 patients (p less than 0.001). The duration of exercise averaged 12 ± 4 minutes for the normal subjects and 9± 4 minutes for the patients (p less than 0.01). The temporal profile of exercise heart rates was dissimilar in the two groups, with patients' rates consistently and progressively less than those of normal subjects. Peak heart rate averaged 152 ± 16 beats per minute for the normal group vs 124 ± 19 beats per minute for the patients (p less than 0.0001); in age-related terms, respectively, 82 ± 6 percent of the maximum heart rate vs 66 ± 10 percent (p less than 0.0001). Thus, patients with chronic fatigue syndrome have normal resting cardiac function but a markedly abbreviated exercise capacity characterized by slow acceleration of heart rate and fatigue of exercising muscles long before peak heart rate is achieved.

RESULTS: The resting heart rate of the patient group was higher, but the maximal heart rate at exhaustion was lower, relative to the control subjects. The maximal workload and maximal oxygen uptake attained by the patients with CFS were almost half those achieved by the control subjects. Analyzing only those persons who performed a maximal exercise test, similar findings were observed.

CONCLUSIONS: When compared with healthy sedentary women, female patients with CFS show a significantly decreased exercise capacity. This could affect their physical abilities to a moderate or severe extent. Reaching the age-predicted target heart rate seemed to be a limiting factor of the patients with CFS in achieving maximal effort, which could be due to autonomic disturbances.

PURPOSE: The purpose of this investigation was to characterize the physiological response profiles of patients with chronic fatigue syndrome (CFS), to an incremental exercise test, performed to the limit of tolerance.

RESULTS: As a group, the CFS patients demonstrated significantly lower cardiovascular as well as ventilatory values at peak exercise, compared with the control group. At similar relative submaximal exercise levels (% peak VO2), the CFS patients portrayed response patterns (trending phenomenon) characterized, in most parameters, by similar intercepts, but either lower (VCO2, HR, O2pulse, VE, VT, PETCO2) or higher (Bf, VE/VCO2) trending kinetics in the CFS compared with the control group. It was found that the primary exercise-related physiological difference between the CFS and the control group was their significantly lower heart rate at any equal relative and at maximal work level. Assuming maximal effort by all (indicated by RER, PETCO2, and subjective exhaustion), these results could indicate either cardiac or peripheral insufficiency embedded in the pathology of CFS patients.

CONCLUSION: We conclude that indexes from cardiopulmonary exercise testing may be used as objective discriminatory indicators for evaluation of patients complaining of chronic fatigue syndrome.

Peckerman's research team at the VA Medical Center in East Orange, N.J., used a sophisticated test to measure how well the heart pumps blood. They gave the test to 16 chronic fatigue syndrome patients, both before and after they exercised. They also tested four non-athletic volunteers. All of the patients' and volunteers' hearts' pumped normally during rest. After exercise, however, 13 of the 16 chronic fatigue patients' hearts pumped less blood than they did at rest.

"Basically we are talking about heart failure," Peckerman tells WebMD. "But chronic fatigue syndrome is a progressive disease. If we were able to detect this in its early stages, it is quite possible there might be a way to treat it."

Emory University cardiologist Joseph I. Miller III, MD, says Peckerman's findings on a potential cause of chronic fatigue syndrome are very interesting. He agrees that these patients have serious heart problems. "Typically we see this in people with three-vessel heart disease," Miller tells WebMD. "A drop in [blood pumped by the heart] during exercise is not a typical response. It is actually a marker of significant coronary artery obstruction."

What's happening to the hearts of people with chronic fatigue syndrome? It's too soon to tell, but Peckerman has a theory. "There is some indication that chronic fatigue syndrome is precipitated by a viral infection," he says. "Some of the viruses that have been suspected have an affinity for the heart."

Here, the prevalence of abnormal Holter monitoring in 67 CFS patients and 78 non-CFS patients matched for age, place and time and absence of other confouding medical diseases were compared. Holter monitors in both CFS and control groups were read by two non-involved cardiologists without clinical knowledge about the patient or place in the study. Dr. Lerner was not a reader of Holter monitors in this study. The prevalence of T-wave abnormalities by Holter monitoring was greater in CFS than in non-CFS patients (p<0.01). The presence of abnormal T-waves at Holter monitoring was "a sensitive indicator of the presence of CFS." The "absence" of these abnormal T-waves made the diagnosis of CFS unlikely (statistical sensitivity 0.96). Light and electron micrographic studies of right ventricular endomyocardial biopsies in these CFS patients showed cardiomyopathic changes. We do not recommend further right ventricular cardiac biopsies in CFS patients since the hearts of CFS patients may be friable and may have an increased likelihood of post-biopsy bleeding.

Summary of Publications 1-3 (Cardiac Involvement in CFS)

This work shows that rapid heart rates at rest, and in some cases, abnormal cardiac wall motion contribute to the light-headedness that many CFS patients experience. Uniformly, abnormal Holter monitoring is present in CFS patients. This additional criterion for diagnosis of CFS illness, namely abnormal Holter monitoring, to the CDC criteria for the diagnosis of CFS does not exclude any CFS patients included in the original CDC definition. The absence of abnormal Holter ECG testing excludes fatigued patients who do not have CFS.A unified theory of the cause of chronic fatigue syndrome. Lerner AM, Zervos M, Dworkin HJ, Chang, CH and O'Neill W. Infectious Diseases in Clinical Practice 1997;6:230-243.

Here, we hypothesize that CFS is a prolonged infectious mononucleosis syndrome in previously healthy (immunocompetent) persons. We further speculate in this early study that prime candidates for cause of CFS are two herpesviruses which cause infectious mononucleosis, Epstein-Barr virus (EBV) and cytomegalovirus (HCMV). We further suggest that studies seeking a single virus cause of CFS, even those studies searching for single-virus EBV or single virus HCMV would conclude in a result of "no cause". Indeed, such negative studies have been done. We suggest that (1997) there may be three causes of CFS, 1) single virus, EBV CFS; 2) single virus HCMV CFS; and 3) EBV-HCMV co-infection CFS. We outline research studies to prove or disprove this new paradigm.\

Here, we emphasize the need of subset classification in the diagnosis and treatment of CFS illness. CFS patients in this study had significant IgG serum antibody titers to cytomegalovirus, but little to no evidence of EBV infection by blood tests. In this study 13 of 18 CFS patients were remarkably improved after 30 days of intravenous ganciclovir (p<0.05). Single virus HCMV CFS in this pilot study was improved by antiviral treatment. There were no side effects from this carefully monitored trial.

Twenty-five patients with CFS illness were treated orally for 6 months with pharmacokinetic doses of valacyclovir (valtrex) in a formulation to give continuous anti-EBV effective blood levels throughout the day. This is the first time such valacyclovir dosing was given. The trial was approved by the U.S. Food and Drug Administration. Patients were carefully monitored for safety by repeated appropriate blood tests. There were no adverse side effects. Sixteen patients with single virus EBV infection were benefitted, but 9 clinically similar CFS patients with EBV-HCMV co-infection were not benefitted. Valacyclovir (valtrex) in the laboratory is effective versus EBV, but it is NOT effective (active) versus HCMV. Therefore, the results strengthen the need for subset classification and appropriate subset-directed antiviral treatment for CFS illness. This, to our knowledge, is the first successful report of valacyclovir treatment for EBV infection.

Eleven CFS patients with EBV-HCMV co-infections were appropriately treated according to their prior subset classification over an 18-month period with antiviral drug treatments. All patients were carefully monitored for safety every 4-6 weeks. Valacyclovir for EBV infection and ganciclovir for HCMV infection were used. There were no significant side effects in CFS patients. All 11 CFS patients in this study were significantly improved.

Summation of Publications 4, 6-8 (Treatment of CFS Illness with Anti-viral Drugs According to Subset Classification)

In these studies, 40 CFS patients were safely treated with antiviral drugs. They were remarkably improved.

This is an especially enlightening study. In many CFS patients in whom our work implies an A) EBV; B) HCMV; or C) EBV-HCMV (co-infection) cause for CFS illness, normal means for diagnosis by blood tests or virus isolation (including those using polymerase chain reactions) are negative, both in our work, reviewed here, and in the careful work of others. In this study, we show a definitive new means of HCMV multiplication in this HCMV subset of CFS patients. The p52 and CM2 HCMV IgM antibodies were present in 16 CFS patients, but were not present in 77 various control patients. In these CFS patients, portions of the HCMV genetic material are synthesized, but remain unassembled into complete virus. These data provide strong evidence for a virus etiology for CFS illness and provide a strong rational for antiviral treatment of CFS patients.

We present the evolution of data describing studies over greater than a decade which support the paradigm that CFS is a prolonged infectious mononucleosis due to Epstein-Barr virus, cytomegalovirus or the two viruses in co-infection undergoing incomplete virus multiplication. The paradigm suggests that the immunocompetent (otherwise healthy) CFS patients' immune defenses do not allow complete virus formation, but only parts of the virus(es) genetic material is expressed. Cardiac involvement of this newly hypothesized method of virus infection leads to rapid heart pumping at rest (tachycardia) and eventually cardiac muscle pump weakening. Specific antiviral treatment has led to remarkable sustained improvement in patient well being so that criteria for the diagnosis of CFS are no longer present. Medical testing by Holter monitoring, MUGA, nuclear stress testing, cardiac biopsy, virus serologic tests and disappearance of symptoms of CFS support this theory.

Here, we report a prospective consecutive case control study from 1987-1999 of cardiac dynamics as measured by radionuclide, ventriculography in 98 CFS patients. Controls were 191 patients with various malignancies who were evaluated in protocols requiring radionuclide ventriculography before initiation of cardiotoxic chemotherapeutic agents. The prevalence of abnormal cardiac wall motion (ACWM) at rest in CFS patients was 10 of 87 patients (11.5%). With stress exercise, 21 CFS patients (24.1%) demonstrated ACWM. Cardiac biopsies in 3 CFS patients with ACWM showed a cardiomyopathy. Among the controls, ACWM at rest was present in 4 of 191 patients (2%) (p=0.0018). A progressive cardiomyopathy often associated with EBV and/or HCMV incomplete virus multiplication is present in CFS patients.

Nondiscocytic erythrocytes in myalgic encephalomyelitis.

Simpson LO.New Zealand Medical Journal 1989; 102: 126-7.

Abstract:

Blood samples from 102 volunteers who believed they suffered from myalgic encephalomyelitis were photographed in a scanning electron microscope at 500x. All identifiable cells were counted and classified on the basis of their shape. The frequency of each cell shape was expressed as a percentage of the total number of cells counted in the sample. The resulting data were compared with that from 52 healthy controls and 99 cases of multiple sclerosis which had been selected randomly by a computer from a panel of 229 cases in a concurrent study. Samples from subjects with myalgic encephalomyelitis had the lowest percentages of normal red cells and the highest incidence of cup forms. The results provide evidence that myalgic encephalomyelitis has an organic cause. Quantitative analysis of red cell shape may assist in the diagnosis of myalgic encephalomyelitis.

You can also ask your doctor for a blood volume test. Every human being requires a certain amount of blood per pound of body weight, and it has been observed that people with fibromyalgia, chronic fatigue syndrome, multiple sclerosis and other illnesses do not have the normal blood volume their body needs to function properly. Doctors aren't normally aware of this.

This test measures the amount of blood in the human body by taking out 5 cc, putting a tracer in it and then putting it back into the body. One hour later, take out 5 cc again and look for the tracer. The thicker the blood and the lower the blood volume, the more tracer you will find.

The analysis of one of my clients stated: "This patient was referred for red cell mass study. The red cell volume is 16.9 ml per kg of body weight. The normal range is 25 to 35 ml per kg. This guy has 36% less blood in his body than the body needs to function." And the doctor hadn't even known the test existed.

If you lost 36% of your blood in an accident, do you think your doctor would tell you that you are alright and should just take up line dancing and get over it? They would rush you to the nearest hospital and start transfusing you with blood. These tragic people with these awful diseases are functioning with anywhere from 7% to 50% less blood than their body needs to function.

According to an article by Maryann Spurgin, Ph.D., New Zealand researcher Dr. L.O. Simpson has theorized that myalgic encephalomyelitis (ME), also known as Chronic Fatigue Immune Deficiency Syndrome (CFIDS), results from "insufficient oxygen availability due to impaired capillary blood flow."

Simpson attributes the impaired capillary blood flow to smaller-than-usual capillaries and to the presence of abnormal red blood cells (nondiscocytes).

In healthy people, most red blood cells are smooth-surfaced and concave-shaped with a donut-like appearance. These discocytes have extra membranes in the concave area that give them the flexibility needed to move through capillary beds, delivering oxygen, nutrients, and chemical messengers to tissue and removing metabolic waste, such as carbon dioxide and lactic acid

"The Role of Red Blood Cell Morphology in the Pathogenesis of ME/CFIDS" by Maryann Spurgin, Ph.D., The CFIDS Chronicle, Summer 1995 discocytes have extra membranes in the concave area that give them the flexibility needed to move through capillary, beds, delivering oxygen, nutrients, and chemical messengers to tissue and removing metabolic waste, such as carbon dioxide and lactic acid. Abnormal red blood cells lack flexibility that allow them to enter tiny capillaries. These nondiscocytes are characterized by a variety of irregularities, including surface bumps or ridges, a cup or basin shape, and altered margins instead of the round shape found in discocytes.

Simpson found that people with ME/CFIDS have higher percentages of nondiscocytes than people' with other chronic illnesses, such as Lupus, multiple sclerosis, Huntington's disease, malaria, and diabetes. In addition, the percentages of cup-shaped somatocytes in ME/CFIDS patients can remain high for months, inhibiting blood flow.

Simpson believes that, in ME/CFIDS, either the mechanism whereby red blood cells revert to the discocyte form is hampered for some reason or that whatever triggered the red blood cells to transform into nondiscocytes remains in effect, albeit unidentified.

Simpson continues, "I found that ME blood filtered poorly - implying that they had a problem with blood flow, particularly at capillary level. In a paper published by New Jersey Medicine, I suggested that ME people might have the anatomical feature of smaller than usual capillary diameters. Such a proposal would help to explain the great variety and variation in distribution of the symptoms reported by ME people."

Other models for the illness have struggled to fit the distinct features of CFIDS, such as exertion intolerance and circulatory dysfunction. Simpson feels impaired blood flow offers a unifying thesis that can explain many of these distinct symptoms. He vividly recalls the unique response to exercise of a patient referred to him. "Two scans were done [SPECT scans] -- pre and post exercise. While the pre-exercise scan showed reduced cerebral blood flow, this was much worse in the post-exercise scan. At that time, the effects of physical activity on red cell shape had not been reported. This shows the extent of ignoring blood rheology factors as determinants of blood flow."

The significance of the concept of 'mean capillary diameter' is that it explains why individuals with similar values for altered red cell shapes do or do not evince symptoms. While the effects on red cell shape of a change in the environment is the same, only those with small capillaries will develop symptoms. As overexertion changes red cell shape in an additive fashion, there will be an accompanying exacerbation of symptoms. It is worth noting that in a CFS patient with SPECT-demonstrated reduced cerebral blood flow in a pre-exercise sample, the cerebral blood flow was further reduced in a post-exercise SPECT scan.

Abstract: The relationship between orthostatic hypotension and chronic fatigue syndrome (CFS) has been reported previously. To study the pathogenesis and management of delayed orthostatic hypotension in patients with CFS, a case comparison study with follow-up of 8 weeks has been designed. A group of 78 patients with CFS (mean age 40 years; 49% men and 51% women), who fulfilled the Centre for Disease Control and Prevention criteria were studied. There were 38 healthy controls (mean age 43 years; 47% men and 53% women). At entry to the study each subject underwent an upright tilt-table test, and clinical and laboratory evaluation. Patients with orthostatic hypotension were offered therapy with sodium chloride (1200 mg) in a sustained-release formulation for 3 weeks, prior to resubmission to the tilt-table testing, and clinical and laboratory evaluation. An abnormal response to upright tilt was observed in 22 of 78 patients with CFS. After sodium chloride therapy for 8 weeks, tilt-table testing was repeated on the 22 patients with an abnormal response at baseline. Of these 22 patients, 10 redeveloped orthostatic hypotension, while 11 did not show an abnormal response to the test and reported an improvement of CFS symptoms. However, those CFS patients who again developed an abnormal response to tilt-test had a significantly reduced plasma renin activity (0.79 pmol/ml per h) compared both with healthy controls (1.29 pmol/ml per h) and with those 11 chronic fatigue patients (1.0 pmol/ml per h) who improved after sodium chloride therapy (p = 0.04). In conclusion, in our study CFS patients who did not respond to sodium chloride therapy were found to have low plasma renin activity. In these patients an abnormal renin-angiotensin-aldosterone system could explain the pathogenesis of orthostatic hypotension and the abnormal response to treatment.

Hyperactivition of an unwanted cellular cascade by the immune-related protein RNase L has been linked to reduced exercise capacity in persons with chronic fatigue syndrome (CFS). This investigation compares exercise capacities of CFS patients with deregulation of the RNase L pathway and CFS patients with normal regulation, while controlling for potentially confounding gender effects. Thirty-five male and seventy-one female CFS patients performed graded exercise tests to voluntary exhaustion. Measures of peak VO2, peak heart rate, body mass index, perceived exertion, and respiratory quotient were entered into a two-way factorial analysis with gender and immune status as independent variables. A significant multivariate main effect was found for immune status (p < 0.01), with no gender effect or interaction. Follow-up analyses identified VO2(peak) as contributing most to the difference. These results implicate abnormal immune activity in the pathology of exercise intolerance in CFS and are consistent with a channelopathy involving oxidative stress and nitric oxide-related toxicity.

Abstract: Cardium thallium-201 single photon emission computerised tomography has been carried out in 10 adult patients with chronic fatigue syndrome. Seven of the patients had defects in the thallium tracer distribution within the left ventricle; this was significantly greater than would have been expected in a normal adult population. Similar abnormal scans have been observed in patients with syndrome X, a condition which has system overlap with chronic fatigue syndrome. It has been suggested that an abnormally high efflux of cellular potassium may be the cause of the abnormal scans in syndrome X, and it is proposed that this mechanism may also have a role to play in chronic fatigue syndrome.

OBJECTIVE: Altered cardiovascular responses to mental an postural stressors have been reported in chronic fatigue syndrome (CFS). This study examined whether those findings may involve changes in baroreceptor reflex functioning. METHODS: Chronotropic baroreceptor reflex (by sequential analysis) and cardiovascular stress responses were recorded during postural (5-minute of active standing) and cognitive (speech task) stress testing in patients with CFS grouped into cases with severe (N = 21) or less severe (N = 22) illness, and in 29 matched control subjects. RESULTS: Patients with CFS had a greater decline in baroreceptor reflex sensitivity (BRS) during standing, although only those with severe CFS were significantly different from the controls. Systolic blood pressure declined during standing in the control group but was maintained in the CFS patients. In contrast, the patients with less severe CFS had blunted increases in blood pressure during the speech task, which could not, however, be explained by inadequate inhibition of the baroreceptor reflex, with all groups showing an appropriate reduction in BRS during the task.CONCLUSIONS: These results indicate that in CFS, deficiencies in orthostatic regulation, but not in centrally mediated stress responses, may involve the baroreceptor reflex. This study also suggests that classifying patients with CFS on illness severity may discriminate between patients with abnormalities in peripheral vs. central mechanisms of cardiovascular stress responses.

Abstract: Eleven patients diagnosed with chronic fatigue syndrome were found to have abnormal left ventricular myocardial dynamics as indicated on MUGA studies. Among the abnormalities noted were low EF at rest or stress (3/11), dilatation of the left ventricle (5/11), and segmental wall motion abnormalities (7/11). One patient had elevated CPK and flat EF response to exercise.

The authors studied the connection between CFS, Ehlers-Danos Syndrome and orthostatic intolerance in a group of adolescent clinic patients. Because of the overlap they found, they suggest that "a careful search for hypermobility and connective tissue abnormalities should be part of the evaluation of patients with CFS and orthostatic intolerance syndromes." The abstract can be read at: http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=10518084&form=6&db=m&Dopt=b

For information on Ehlers-Danos Syndrome, see http://www.ednf.org/ and http://www.stepstn.com/cgi-win/nord.exe?proc=GetDocument&rectype=0&recnum=240 Orthostatic intolerance, a common symptom in CFS, is the general inability to be upright for any length of time without various symptoms, including lightheadedness, dizziness, fainting, and nausea. The most well-publicized type of OI is neurally-mediated hypotension (NMH), but many people with OI do not test positive for blood pressure abnormalities.

OBJECTIVE: To compare the cardiovascular response during postural challenge of patients with fibromyalgia (FM) to those with chronic fatigue syndrome (CFS).

METHODS: Age and sex matched patients were studied, 38 with FM, 30 with CFS, and 37 healthy subjects. Blood pressure (BP) and heart rate (HR) were recorded during 10 min of recumbence and 30 min of head-up tilt. Differences between successive BP values and the last recumbent BP, their average, and standard deviation (SD) were calculated. Time curves of BP differences were analyzed by computer and their outline ratios (OR) and fractal dimensions (FD) were measured. HR differences were determined similarly. Based on the latter measurements, each subject's discriminant score (DS) was computed.

CONCLUSION: The DS confers numerical expression to the cardiovascular response during postural challenge. DS values in FM were significantly different from DS in CFS, suggesting that homeostatic responses in FM and CFS are dissimilar. This observation challenges the hypothesis that FM and CFS share a common derangement of the stress-response system.

The use of symptoms generated by head up tilt (HUT) is not a useful tool in identifying chronic fatigue syndrome (CFS). We investigated whether heart rate variability (HRV) assessed early during HUT might be useful. A sample of 46 female subjects (24 with CFS and 22 sedentary, age-matched healthy controls; CON) who had exhibited no difference in time to syncope during tilt was examined for HRV responses to 10 min of 70 degrees HUT after 5 min of baseline in the supine position. HRV data were analyzed by the method of coarse graining spectral analysis. Variables compared between groups included mean and standard deviation (SD(RRI)) of RR intervals (RRI), amplitudes of low- (A(LF); 0.04-0.15 Hz) and high-frequency (A(HF); >0.15 Hz) harmonic as well as aperiodic, fractal (A(FR); 1/f(beta)) spectral components, the spectral exponent beta, and the difference in these values between baseline and HUT for each subject. In the supine baseline, only mean RRI was significantly (P < 0.01) lower in CFS than in CON. During HUT, however, mean RRI (P < 0.01), SD(RRI) (P < 0.01), A(HF) (P < 0.05), and A(FR) (P < 0.01) were significantly lower in CFS than in CON. When the difference in values between baseline and HUT for each subject was examined, only the difference for A(FR) (deltaA(FR)) was significantly (P < 0.01) lower in CFS than in CON, suggesting that A(FR)is a disease-specific response of HRV to HUT. When a cut-off level was set to deltaA(FR) = -2.7 msec, the sensitivity and the specificity in differentiating CFS from controls were 90% and 72%, respectively. The data suggest that a decrease in aperiodic fractal component of HRV in response to HUT can be used to differentiate patients with CFS from CON.

The objective was to determine the nature of autonomic and vasomotor changes in adolescent patients with orthostatic tachycardia associated with the chronic fatigue syndrome (CFS) and the postural orthostatic tachycardia syndrome (POTS).

Continuous electrocardiography and arterial tonometry was used to investigate the heart rate and blood pressure responses before and 3-5 min after head-up tilt in 22 adolescents with POTS and 14 adolescents with CFS, compared with control subjects comprising 10 healthy adolescents and 20 patients with simple faint. Heart rate and blood pressure variability, determined baroreceptor function using transfer function analysis, and measured cardiac vagal and adrenergic autonomic responses were calculated using timed breathing and the quantitative Valsalva maneuver.

Two of 10 healthy controls and 14 of 20 simple faint patients experienced vasovagal syncope during head-up tilt. By design, all CFS and POTS patients experienced orthostatic tachycardia, often associated with hypotension. R-R interval and heart rate variability were decreased in CFS and POTS patients compared with control subjects and remained decreased with head-up tilt. Low-frequency (0.05-0.15 Hz) blood pressure variability reflecting vasomotion was increased in CFS and POTS patients compared with control subjects and increased further with head-up tilt.

This was associated with depressed baroreflex transfer indicating baroreceptor attenuation through defective vagal efferent response. Only the sympathetic response remained. Heart rate variability declined progressively from normal healthy control subjects through syncope to POTS to CFS patients. Timed breathing and Valsalva maneuver were most often normal in CFS and POTS patients, although abnormalities in select individuals were found.

Heart rate and blood pressure regulation in POTS and CFS patients are similar and indicate attenuated efferent vagal baroreflex associated with increased vasomotor tone. Loss of beat-to-beat heart rate control may contribute to a destabilized blood pressure resulting in orthostatic intolerance. The dysautonomia of orthostatic intolerance in POTS and in chronic fatigue [syndrome] are similar.